Amenorrhea: Classification

WHO classification of amenorrhea.

WHO stage	Definition	Examples	Endocrinological diagnostics
I	Hypogonadotropic normoprolactinemic ovarian failure = hypothalamic-hypogonadotropic (-hypophyseal hypofunction)	Competitive sports, eating disorders (e.g., anorexia nervosa/anorexia nervosa), Kallmann syndrome (hypogonadotropic hypogonadism + anosmia/loss of sense of smell), Sheehan syndrome (loss of function of the anterior lobe of the pituitary gland, which usually occurs postpartum (after childbirth))	FSH ↓ LH ↓ E2 (estradiol) ↓ Progestin test negative, i.e., progestin-negative amenorrhea. Estrogen testagen test positive
II	Normogonadotropic normoprolactinemic ovarian failure = hypothalamic-pituitary dysfunction	Polycystic ovary syndrome (PCO syndrome), follicular persistence (failure of the follicle to rupture and thus the egg follicle to persist), hypothyroidism (hypothyroidism)	Androgens (testosterone, DHEAS, androstenedione,17-OH-progesterone). If necessary, dexamethasone inhibition test to distinguish functional from autonomous hyperandrogenemia (e.g., in the setting of an androgen-producing tumor) Cortisol Progestin test negative, i.e., progestin-negative amenorrhea.
III	hypergonadotropic ovarian failure	Gonadal dysgenesis, climacterium praecox (premature menopause; premature ovarian failure = POF; premature menopause), menopause, Turner syndrome (synonym: Ullrich-Turner syndrome); girls/women with this peculiarity have only one functional X chromosome instead of the usual two (monosomy X)), condition after chemotherapy	FSH ↑ LH ↑ E2 (estradiol) ↓ Progestin test negative, i.e., progestin-negative amenorrhea. Estrogen testagen test positive
IV	Anatomically determined amenorrhea = congenital or acquired anomaly in the genital tract, endometrium, uterus, or vagina	Primary: hymenal atresia (congenital malformation of the hymen (hymen) in which the vagina (vagina) is completely closed by the hymen), uterine malformation/agenesis, Secondary: Asherman syndrome, endometrial atrophy (atrophy of the endometrium), cervical stenosis.
V	Hyperprolactinemic ovarian failure with tumor	Prolactinoma (benign neoplasm of the anterior pituitary (pituitary gland)).	Prolactin ↑ Progestin test positive or negative Estrogen testagen test positive
VI	Hyperprolactinemic ovarian insufficiency without tumor (dysfunctional hyperprolactinemia)	Hypothyroidism (hypothyroidism) or latent hypothyroidism, drug-induced hyperprolactinemia	Prolactin ↑ TSH ↑ Progestin test positive or negative Estrogen testagen test positive
VII	Normoprolactinemic hypothalamic-pituitary dysfunction (hypogonadotropic due to organic causes (compression).	Pituitary tumor (tumor of the pituitary gland, e.g., craniopharyngioma)